Thioctic acid is a substance found in nature, both in animal and plant cells, as the R enantiomer; it is a coenzyme for the oxidative decarboxylation of α-ketocarboxylic acids and an antioxidant able to regenerate vitamin C, vitamin E, glutathione and coenzyme Q10. Moreover, the raceme is employed for the treatment of hepatic disorders and neuropathies and in addition demonstrates cytoprotective anti-inflammatory and analgesic activity.
Syntheses of the racemic crude and optically active acid are conducted using methods described in Eur. J. 1998, 1949; Fadnavis et Al., Tetrahedron Asym., 1998, 9 4109, Dhar et Al., J. Org. Chem., 1992, 57, 1699, WO0230918, WO0230919.
The usual methods for purifying thioctic acid consist of recrystallization from solvents for example from n-pentane, cyclohexane, ethyl ether, ethyl acetate, etc. Thioctic acid is then recovered by filtration and centrifugation, and subsequently dried (J. Chem. Soc. Perkin Trans. 1 1988, 9, Segre et Al., J. Am. Chem. Soc., 1957, 3503; Walton et Al., J. Am. Chem. Soc., 1955, 77, 5144, Acker et Al., J. Am. Chem. Soc., 1954, 76, 6483).
The residual solvents present in the purification processes cannot be completely removed.
The active principles should not contain residual solvents in quantities exceeding safety levels.
To overcome this drawback a thioctic acid purification process was proposed in U.S. Pat. No. 6,462,202, conducted in the absence of organic solvents.
This process comprises in particular the following steps:    a) dissolving the thioctic acid in an aqueous alkaline solution or alternatively dissolving a salt thereof in water and suitably adjusting to an alkaline pH,    b) removing any solid impurities from the solution obtained in step (a),    c) acidifying the aqueous solution from step (a) or (b) to a pH between pH 1.0 and 5.0.    d) isolating the thioctic acid by known methods.
Even though this process presents considerable advantages, the thioctic acid purity was found not to be high because at the aforestated acid pHs, polymerization of the thioctic acid causes appreciable quantities of impurities to form, traceable by dissolving said product in chloroform.
A product with such characteristics does not comply with requirements that would allow its sale for the preparation of pharmaceutical formulations.
The need was therefore felt to provide a purification process for thioctic acid that would not present the inconveniences of the aforesaid process.